We have found that clinically significant depressions occur in almost half of the acute stroke patients and that these depressions last more than 6 months in more than three-quarters of the patients. We have also found that the patients with the most severe depressions usually have a left frontal lobe infarction and there is a strong correlation between the proximity of the lesion to the frontal pole on CT scan and the severity of depression. Our laboratory investigations have demonstrated the behavioral and biochemical response to experimental stroke in rats is asymmetrical, even though right and left hemisphere lesions appear to be comparable. We have also demonstrated in the laboratory that the amount of catecholamine depletion and the degree of spontaneous hyperactivity are greatest when the lesion is closer to the frontal pole. These experiments suggest that mood disorders after stroke may be a behavioral consequence of changes in brain biogenic amine concentrations. The studies herein propose to extend these observations in the clinic and laboratory. The clinical studies will confirm or refute our earlier observation as well as extend the breadth of investigation to include both PET scan imaging of depressed and non-depressed stroke patients and analysis of spinal fluid catecholamine metabolites. Our findings on the course and symptoms of these disorders will be compared with control groups and we will investigate whether the depressed stroke patients have a stronger family history of mood disorder than non-depressed stroke patients. A computer decision support system will be set up which would help practitioners decide on the likelihood of a patient developing significant depression and the most appropriate treatment. Finally, from a practical clinical viewpoint we will determine whether post-stroke depressions can be effectively treated with nortriptyline. The proposed laboratory experiments will investigate the phenomenon of behavioral and biochemical lateralization in rats and extend our earlier observations of biochemical changes to include turnover-receptor studies and improve our behavioral measures by utilizing computerized activity chambers. The lateralized effect of cortical lesions on scheduled behavior and the responsiveness to intraventricular pharmacological treatment as well as the developmental aspect of this phenomenon will also be investigated.